title: Automated test of behavioral flexibility in mice using a behavioral sequencing task in IntelliCage.
abstract: There has been a long-standing need to develop efficient and standardized behavioral test methods for evaluating higher-order brain functions in mice. Here, we developed and validated a behavioral flexibility test in mice using IntelliCage, a fully automated behavioral analysis system for mice in a group-housed environment. We first developed a "behavioral sequencing task" in the IntelliCage that enables us to assess the learning ability of place discrimination and behavioral sequence for reward acquisition. In the serial reversal learning using the task, the discriminated spatial patterns of the rewarded and never-rewarded places were serially reversed, and thus, mice were accordingly expected to realign the previously acquired behavioral sequence. In general, the tested mice showed rapid acquisition of the behavioral sequencing task and behavioral flexibility in the subsequent serial reversal stages both in intra- and inter-session analyses. It was found that essentially the same results were obtained among three different laboratories, which confirm the high stability of the present test protocol in different strains of mice (C57BL/6, DBA/2, and ICR). In particular, the most trained cohort of C57BL/6 mice achieved a markedly rapid adaptation to the reversal task in the final phase of the long-term serial reversal test, which possibly indicated that the mice adapted to the "reversal rule" itself. In conclusion, the newly developed behavioral test was shown to be a valid assay of behavioral flexibility in mice, and is expected to be utilized in tests of mouse models of cognitive deficits.
authors.affiliation: Laboratory of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Endo
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Maekawa
authors.forename: Vootele
authors.initials: V
authors.lastname: Võikar
authors.forename: Asahi
authors.initials: A
authors.lastname: Haijima
authors.forename: Yukari
authors.initials: Y
authors.lastname: Uemura
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wataru
authors.initials: W
authors.lastname: Miyazaki
authors.forename: Shigetomo
authors.initials: S
authors.lastname: Suyama
authors.forename: Kuniko
authors.initials: K
authors.lastname: Shimazaki
authors.forename: David P
authors.initials: DP
authors.lastname: Wolfer
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yada
authors.forename: Chiharu
authors.initials: C
authors.lastname: Tohyama
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Lipp
authors.forename: Masaki
authors.initials: M
authors.lastname: Kakeyama
mesh_terms: D000818:Animals; D057205:Automation, Laboratory / Q000379:methods*; D004193:Discrimination Learning; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008813:Mice, Inbred ICR; D023421:Models, Animal; D012193:Reversal Learning; D012201:Reward; D012691:Serial Learning; D013045:Species Specificity